Malaria is naturally transmitted by the bite of a female Anopheles
mosquito. When a mosquito bites an infected person, a small
amount of blood is taken, which contains malaria parasites. These
develop within the mosquito, and about one week later, when the
mosquito takes its next blood meal, the parasites are injected with
the mosquito's saliva into the person being bitten. After a period
of between 2 weeks and several months (occasionally years) spent in
the liver, the malaria parasites start to multiply within red blood cells,
causing symptoms that include fever and headache. In severe cases, the disease
worsens, leading to coma and
death.

A wide variety of antimalarial
drugs are available to treat malaria. In the last 5 years,
treatment of P. falciparum infections in endemic countries has been transformed by the
use of combinations of drugs containing an artemisinin derivative. Severe malaria is
treated with intravenous or intramuscular quinine or, increasingly,
the artemisinin
derivative artesunate[6].
Several drugs are also available to prevent malaria in travellers
to malaria-endemic countries (prophylaxis). Resistance has
developed to several antimalarial drugs, most notably chloroquine[7].

Malaria transmission can be reduced by preventing mosquito bites
with mosquito nets
and insect
repellents, or by mosquito control measures such as spraying insecticides inside
houses and draining standing water where mosquitoes lay their
eggs.

Although many are under development, the challenge of producing
a widely available vaccine
that provides a high level of protection for a sustained period is
still to be met[8].

Signs and
symptoms

Symptoms of malaria include fever, shivering, arthralgia (joint pain), vomiting, anemia (caused by hemolysis), hemoglobinuria, retinal damage,[10] and convulsions. The classic
symptom of malaria is cyclical occurrence of sudden coldness
followed by rigor and then fever and sweating lasting
four to six hours, occurring every two days in P. vivax
and P. ovale infections, while every three for P.
malariae.[11]P. falciparum can have recurrent fever every 36–48 hours
or a less pronounced and almost continuous fever. For reasons that
are poorly understood, but that may be related to high intracranial pressure, children
with malaria frequently exhibit abnormal posturing, a sign
indicating severe brain damage.[12]
Malaria has been found to cause cognitive impairments, especially
in children. It causes widespread anemia during a period of rapid brain
development and also direct brain damage. This neurologic damage
results from cerebral malaria to which children are more
vulnerable.[13][14]
Cerebral malaria is associated with retinal whitening,[15] which
may be a useful clinical sign in distinguishing malaria from other
causes of fever.[16]

Severe malaria is almost exclusively caused by P.
falciparum infection, and usually arises 6–14 days after
infection.[17]
Consequences of severe malaria include coma and death if untreated—young children and
pregnant women are especially vulnerable. Splenomegaly (enlarged spleen), severe headache, cerebral ischemia, hepatomegaly
(enlarged liver), hypoglycemia, and hemoglobinuria with renal failure may
occur. Renal failure may cause blackwater fever, where hemoglobin
from lysed red blood cells leaks into the urine. Severe malaria can
progress extremely rapidly and cause death within hours or
days.[17]
In the most severe cases of the disease, fatality rates can exceed
20%, even with intensive care and treatment.[18] In
endemic areas, treatment is often less satisfactory and the overall
fatality rate for all cases of malaria can be as high as one in
ten.[19] Over
the longer term, developmental impairments have been documented in
children who have suffered episodes of severe malaria.[20]

Chronic malaria is seen in both P. vivax and P.
ovale, but not in P. falciparum. Here, the disease
can relapse months or years after exposure, due to the presence of
latent parasites in the liver. Describing a case of malaria as
cured by observing the disappearance of parasites from the
bloodstream can, therefore, be deceptive. The longest incubation
period reported for a P. vivax infection is 30 years.[17]
Approximately one in five of P. vivax malaria cases in temperate areas involve overwintering by
hypnozoites (i.e., relapses begin the year after the mosquito
bite).[21]

Causes

A Plasmodium sporozoite traverses the cytoplasm of a
mosquito midgut epithelial cell in this false-color electron micrograph.

Malaria
parasites

Malaria parasites are members of the genus Plasmodium (phylum
Apicomplexa). In
humans malaria is caused by P. falciparum, P.
malariae, P. ovale, P. vivax
and P. knowlesi.[22][23]P. falciparum is the most common cause of infection and is
responsible for about 80% of all malaria cases, and is also
responsible for about 90% of the deaths from malaria.[24]
Parasitic Plasmodium species also infect birds, reptiles,
monkeys, chimpanzees and rodents.[25] There
have been documented human infections with several simian species of malaria, namely
P. knowlesi, P. inui, P. cynomolgi,[26]P. simiovale, P. brazilianum, P.
schwetzi and P. simium; however, with the exception
of P. knowlesi, these are mostly of limited public health
importance.[27]

Mosquito
vectors and the Plasmodium life cycle

The parasite's primary (definitive) hosts and transmission vectors are female mosquitoes of the Anopheles genus, while
humans and other vertebrates are secondary hosts. Young mosquitoes
first ingest the malaria parasite by feeding on an infected human
carrier and the infected Anopheles mosquitoes carry
Plasmodiumsporozoites in their salivary glands.
A mosquito becomes infected when it takes a blood meal from an
infected human. Once ingested, the parasite gametocytes taken up in
the blood will further differentiate into male or female gametes and
then fuse in the mosquito gut. This produces an ookinete that penetrates
the gut lining and produces an oocyst in the gut wall. When the oocyst
ruptures, it releases sporozoites that migrate through the
mosquito's body to the salivary glands, where they are then ready
to infect a new human host. This type of transmission is
occasionally referred to as anterior station transfer.[28] The
sporozoites are injected into the skin, alongside saliva, when the
mosquito takes a subsequent blood meal.

Only female mosquitoes feed on blood, thus males do not transmit
the disease. The females of the Anopheles genus of
mosquito prefer to feed at night. They usually start searching for
a meal at dusk, and will continue throughout the night until taking
a meal. Malaria parasites can also be transmitted by blood
transfusions, although this is rare.[29]

Pathogenesis

The life cycle of malaria parasites in the human body. A mosquito
infects a person by taking a blood meal. First, sporozoites enter
the bloodstream, and migrate to the liver. They infect liver cells
(hepatocytes), where they multiply into merozoites, rupture the
liver cells, and escape back into the bloodstream. Then, the
merozoites infect red blood cells, where they develop into ring
forms, then trophozoites (a feeding stage), then schizonts (a
reproduction stage), then back into merozoites. Sexual forms called
gametocytes are also produced, which, if taken up by a mosquito,
will infect the insect and continue the life cycle.

Malaria in humans develops via two phases: an exoerythrocytic
and an erythrocytic phase. The exoerythrocytic phase involves
infection of the hepatic system, or liver, whereas the erythrocytic
phase involves infection of the erythrocytes, or red blood cells.
When an infected mosquito pierces a person's skin to take a blood
meal, sporozoites in the mosquito's saliva enter
the bloodstream and migrate to the liver. Within 30 minutes of being introduced into
the human host, the sporozoites infect hepatocytes, multiplying asexually and
asymptomatically for a period of 6–15 days. Once in the liver,
these organisms differentiate to yield thousands of merozoites, which, following rupture of
their host cells, escape into the blood and infect red blood cells,
thus beginning the erythrocytic stage of the life cycle.[30] The
parasite escapes from the liver undetected by wrapping itself in
the cell membrane of the infected host liver cell.[31]

Within the red blood cells, the parasites multiply further,
again asexually, periodically breaking out of their hosts to invade
fresh red blood cells. Several such amplification cycles occur.
Thus, classical descriptions of waves of fever arise from
simultaneous waves of merozoites escaping and infecting red blood
cells.

Some P. vivax and P. ovale sporozoites do not
immediately develop into exoerythrocytic-phase merozoites, but
instead produce hypnozoites that remain dormant for periods ranging
from several months (6–12 months is typical) to as long as three
years. After a period of dormancy, they reactivate and produce
merozoites. Hypnozoites are responsible for long incubation and
late relapses in these two species of malaria.[32]

The parasite is relatively protected from attack by the body's
immune system
because for most of its human life cycle it resides within the
liver and blood cells and is relatively invisible to immune
surveillance. However, circulating infected blood cells are
destroyed in the spleen. To
avoid this fate, the P. falciparum parasite displays
adhesive proteins on the
surface of the infected blood cells, causing the blood cells to
stick to the walls of small blood vessels, thereby sequestering the
parasite from passage through the general circulation and the
spleen.[33]
This "stickiness" is the main factor giving rise to hemorrhagic complications of malaria. High endothelial venules (the
smallest branches of the circulatory system) can be blocked by the
attachment of masses of these infected red blood cells. The
blockage of these vessels causes symptoms such as in placental and
cerebral malaria. In cerebral malaria the sequestrated red blood
cells can breach the blood brain barrier possibly
leading to coma.[34]

Although the red blood cell surface adhesive proteins (called
PfEMP1, for Plasmodium falciparum erythrocyte membrane
protein 1) are exposed to the immune system, they do not serve as
good immune targets, because of their extreme diversity; there are
at least 60 variations of the protein within a single parasite and
effectively limitless versions within parasite populations.[33]
The parasite switches between a broad repertoire of PfEMP1 surface
proteins, thus staying one step ahead of the pursuing immune
system.

Some merozoites turn into male and female gametocytes. If a mosquito pierces the skin
of an infected person, it potentially picks up gametocytes within
the blood. Fertilization and sexual recombination of the parasite
occurs in the mosquito's gut, thereby defining the mosquito as the
definitive host of the disease. New
sporozoites develop and travel to the mosquito's salivary gland,
completing the cycle. Pregnant women are especially attractive to
the mosquitoes,[35] and
malaria in pregnant women is an important cause of stillbirths, infant
mortality and low birth weight,[36]
particularly in P. falciparum infection, but also in other
species infection, such as P. vivax.[37]

Diagnosis

Blood smear from a P. falciparumculture (K1
strain). Several red blood cells have ring stages inside them.
Close to the center there is a schizont and on the left a
trophozoite.

Since Charles Laveran first visualised the malaria parasite in
blood in 1880,[38]
the mainstay of malaria diagnosis has been the microscopic
examination of blood.

Fever and septic shock are commonly misdiagnosed as severe
malaria in Africa, leading to
a failure to treat other life-threatening illnesses. In
malaria-endemic areas, parasitemia does not ensure a diagnosis of
severe malaria, because parasitemia can be incidental to other
concurrent disease. Recent investigations suggest that malarial retinopathy is better
(collective sensitivity of 95% and specificity of 90%) than any
other clinical or laboratory feature in distinguishing malarial
from non-malarial coma.[39]

Although blood is the sample most frequently used to make a
diagnosis, both saliva and urine have been investigated as
alternative, less invasive specimens.[38]

Symptomatic diagnosis

Areas that cannot afford even simple laboratory diagnostic tests
often use only a history of subjective fever as the indication to
treat for malaria. Using Giemsa-stained blood smears from children
in Malawi, one study showed that when clinical predictors (rectal
temperature, nailbed pallor, and splenomegaly) were used as
treatment indications, rather than using only a history of
subjective fevers, a correct diagnosis increased from 21% to 41% of
cases, and unnecessary treatment for malaria was significantly
decreased.[40]

Microscopic examination
of blood films

The most economic, preferred, and reliable diagnosis of malaria
is microscopic examination of blood films because each of the four major
parasite species has distinguishing characteristics. Two sorts of
blood film are traditionally used. Thin films are similar to usual
blood films and allow species identification because the parasite's
appearance is best preserved in this preparation. Thick films allow
the microscopist to screen a larger volume of blood and are about
eleven times more sensitive than the thin film, so picking up low
levels of infection is easier on the thick film, but the appearance
of the parasite is much more distorted and therefore distinguishing
between the different species can be much more difficult. With the
pros and cons of both thick and thin smears taken into
consideration, it is imperative to utilize both smears while
attempting to make a definitive diagnosis.[41]

From the thick film, an experienced microscopist can detect
parasite levels (or parasitemia) down to as low as 0.0000001%
of red blood cells. Diagnosis of species can be difficult because
the early trophozoites ("ring form") of all four species look
identical and it is never possible to diagnose species on the basis
of a single ring form; species identification is always based on
several trophozoites.

Field
tests

In areas where microscopy is not available, or where laboratory
staff are not experienced at malaria diagnosis, there are antigen detection tests
that require only a drop of blood.[42]
Immunochromatographic tests (also called: Malaria Rapid Diagnostic
Tests, Antigen-Capture Assay or "Dipsticks") have been developed,
distributed and fieldtested. These tests use finger-stick or venous
blood, the completed test takes a total of 15–20 minutes, and a
laboratory is not needed. The threshold of detection by these rapid
diagnostic tests is in the range of 100 parasites/µl of blood
compared to 5 by thick film microscopy. The first rapid diagnostic
tests were using P. falciparumglutamate dehydrogenase as
antigen.[43]
PGluDH was soon replaced by P.falciparumlactate
dehydrogenase, a 33 kDa oxidoreductase [EC 1.1.1.27]. It is the
last enzyme of the glycolytic pathway, essential for ATP generation and one of the
most abundant enzymes expressed by P.falciparum. PLDH does
not persist in the blood but clears about the same time as the
parasites following successful treatment. The lack of antigen
persistence after treatment makes the pLDH test useful in
predicting treatment failure. In this respect, pLDH is similar to
pGluDH. The OptiMAL-IT assay can distinguish between P.
falciparum and P. vivax because of antigenic
differences between their pLDH isoenzymes. OptiMAL-IT will reliably
detect P. falciparum down to 0.01% parasitemia and other species down to 0.1%.
Paracheck-Pf will detect parasitemias down to 0.002% but will not
distinguish between falciparum and non-falciparum malaria. Parasite
nucleic acids are detected using polymerase chain reaction.
This technique is more accurate than microscopy. However, it is
expensive, and requires a specialized laboratory. Moreover, levels
of parasitemia are not necessarily correlative with the progression
of disease, particularly when the parasite is able to adhere to
blood vessel walls. Therefore more sensitive, low-tech diagnosis
tools need to be developed in order to detect low levels of
parasitemia in the field.

Molecular
methods

Molecular methods are available in some clinical laboratories
and rapid real-time assays (for example, QT-NASBA based on
the polymerase chain reaction)[44] are
being developed with the hope of being able to deploy them in
endemic areas.

Rapid
antigen tests

OptiMAL-IT will reliably detect falciparum down to
0.01% parasitemia
and non-falciparum down to 0.1%. Paracheck-Pf
will detect parasitemias down to 0.002% but will not distinguish
between falciparum and non-falciparum malaria.
Parasite nucleic acids are detected using polymerase chain reaction.
This technique is more accurate than microscopy. However, it is
expensive, and requires a specialized laboratory. Moreover, levels
of parasitemia are not necessarily correlative with the progression
of disease, particularly when the parasite is able to adhere to
blood vessel walls. Therefore more sensitive, low-tech diagnosis
tools need to be developed in order to detect low levels of
parasitaemia in the field. [45]

Prevention

Anopheles
albimanus mosquito feeding on a human arm. This mosquito is a
vector of malaria and mosquito control is a very effective way of
reducing the incidence of malaria.

Methods used to prevent the spread of disease, or to protect
individuals in areas where malaria is endemic, include prophylactic
drugs, mosquito eradication, and the prevention of mosquito bites.
The continued existence of malaria in an area requires a
combination of high human population density, high mosquito
population density, and high rates of transmission from humans to
mosquitoes and from mosquitoes to humans. If any of these is
lowered sufficiently, the parasite will sooner or later disappear
from that area, as happened in North America, Europe and much of Middle East. However, unless the parasite
is eliminated from the whole world, it could become re-established
if conditions revert to a combination that favors the parasite's
reproduction. Many countries are seeing an increasing number of
imported malaria cases due to extensive travel and migration.

Many researchers argue that prevention of malaria may be more
cost-effective than treatment of the disease in the long run, but
the capital costs required are out of reach of many of the world's
poorest people. Economic adviser Jeffrey Sachs estimates that malaria can
be controlled for US$3 billion in aid per year.

The distribution of funding varies among countries. Countries
with large populations do not receive the same amount of support.
The 34 countries that received a per capita annual support of less
than $1 included some of the poorest countries in Africa.

Brazil, Eritrea, India, and Vietnam have, unlike many other
developing nations, successfully reduced the malaria burden. Common
success factors included conducive country conditions, a targeted
technical approach using a package of effective tools, data-driven
decision-making, active leadership at all levels of government,
involvement of communities, decentralized implementation and
control of finances, skilled technical and managerial capacity at
national and sub-national levels, hands-on technical and
programmatic support from partner agencies, and sufficient and
flexible financing.[46]

Vector
control

Efforts to eradicate malaria by
eliminating mosquitoes have been successful in some areas. Malaria
was once common in the United States and southern Europe, but vector control
programs, in conjunction with the monitoring and treatment of
infected humans, eliminated it from those regions. In some areas,
the draining of wetland breeding grounds and better sanitation were
adequate. Malaria was eliminated from the northern parts of the USA
in the early 20th century by such methods, and the use of the pesticideDDT eliminated it from the South by 1951.[47]
In 2002, there were 1,059 cases of malaria reported in the US,
including eight deaths, but in only five of those cases was the
disease contracted in the United States.

Before DDT, malaria was successfully eradicated or controlled
also in several tropical areas by removing or poisoning the
breeding grounds of the mosquitoes or the aquatic habitats of the
larva stages, for example by filling or applying oil to places with
standing water. These methods have seen little application in
Africa for more than half a century.[48] In
the 1950s and 1960s, there was a major public health effort to
eradicate malaria worldwide by selectively targeting mosquitoes in
areas where malaria was rampant.[49]
However, these efforts have so far failed to eradicate malaria in
many parts of the developing world—the problem is most prevalent in
Africa.

Sterile insect technique is
emerging as a potential mosquito control method. Progress towards
transgenic, or genetically modified,
insects suggest that wild mosquito populations could be made
malaria-resistant. Researchers at Imperial College London created
the world's first transgenic malaria mosquito,[50] with
the first plasmodium-resistant species announced by a team at Case Western Reserve
University in Ohio in
2002.[51]
Successful replacement of current populations with a new
genetically modified population, relies upon a drive mechanism,
such as transposable
elements to allow for non-Mendelian inheritance of the gene of
interest. However, this approach contains many difficulties and
success is a distant prospect.[52] An
even more futuristic method of vector control is the idea that lasers could be used to kill flying
mosquitoes.[53]

Prophylactic
drugs

Several drugs, most of which are also used for treatment of
malaria, can be taken preventively. Generally, these drugs are
taken daily or weekly, at a lower dose than would be used for
treatment of a person who had actually contracted the disease. Use
of prophylactic drugs is seldom practical for full-time residents
of malaria-endemic areas, and their use is usually restricted to
short-term visitors and travelers to malarial regions. This is due
to the cost of purchasing the drugs, negative side effects from long-term use, and
because some effective anti-malarial drugs are difficult to obtain
outside of wealthy nations.

Quinine was used starting
in the 17th century as a prophylactic against malaria. The
development of more effective alternatives such as quinacrine, chloroquine, and primaquine in the 20th
century reduced the reliance on quinine. Today, quinine is still
used to treat chloroquine resistant Plasmodium falciparum, as
well as severe and cerebral stages of malaria, but is not generally
used for prophylaxis.

Modern drugs used preventively include mefloquine (Lariam), doxycycline (available
generically), and the combination of atovaquone and proguanil hydrochloride (Malarone).
The choice of which drug to use depends on which drugs the
parasites in the area are resistant to, as well as side-effects
and other considerations. The prophylactic effect does not begin
immediately upon starting taking the drugs, so people temporarily
visiting malaria-endemic areas usually begin taking the drugs one
to two weeks before arriving and must continue taking them for 4
weeks after leaving (with the exception of atovaquone proguanil
that only needs be started 2 days prior and continued for 7 days
afterwards).

The use of prophylactic drugs where malaria-bearing mosquitoes
are present may encourage the development of partial immunity.[54]

Indoor
residual spraying

Indoor residual spraying (IRS) is the practice of spraying
insecticides on the interior walls of homes in malaria affected
areas. After feeding, many mosquito species rest on a nearby
surface while digesting the bloodmeal, so if the walls of dwellings
have been coated with insecticides, the resting mosquitos will be
killed before they can bite another victim, transferring the
malaria parasite.

The first pesticide used for IRS was DDT.[47]
Although it was initially used exclusively to combat malaria, its
use quickly spread to agriculture. In time, pest-control, rather
than disease-control, came to dominate DDT use, and this
large-scale agricultural use led to the evolution of resistant mosquitoes in many
regions. The DDT resistance shown by Anopheles mosquitoes can be
compared to antibiotic resistance shown by bacteria. The overuse of
anti-bacterial soaps and antibiotics led to antibiotic resistance
in bacteria, similar to how overspraying of DDT on crops led to DDT
resistance in Anopheles mosquitoes. During the 1960s, awareness of
the negative consequences of its indiscriminate use increased,
ultimately leading to bans on agricultural applications of DDT in
many countries in the 1970s. Since the use of DDT has been limited
or banned for agricultural use for some time, DDT may now be more
effective as a method of disease-control.

Although DDT has never been banned for use in malaria control
and there are several other insecticides suitable for IRS, some
advocates have claimed that bans are responsible for tens of
millions of deaths in tropical countries where DDT had once been
effective in controlling malaria. Furthermore, most of the problems
associated with DDT use stem specifically from its industrial-scale
application in agriculture, rather than its use in public health.[55]

The World Health Organization
(WHO) currently advises the use of 12 different insecticides in IRS
operations. These include DDT and a series of alternative
insecticides (such as the pyrethroids permethrin and deltamethrin), to combat malaria in areas
where mosquitoes are DDT-resistant and to slow the evolution of
resistance.[56] This
public health use of small amounts of DDT is permitted under the Stockholm Convention on Persistent
Organic Pollutants (POPs), which prohibits the agricultural use
of DDT.[57]
However, because of its legacy, many developed countries discourage
DDT use even in small quantities.[58][59]

One problem with all forms of Indoor Residual Spraying is
insecticide resistance via evolution of
mosquitos. According to a study published on Mosquito Behavior and
Vector Control, mosquito species that are affected by IRS are
endophilic species (species that tend to rest and live indoors),
and due to the irritation caused by spraying, their evolutionary
descendants are trending towards becoming exophilic (species that
tend to rest and live out of doors), meaning that they are not as
affected—if affected at all—by the IRS, rendering it somewhat
useless as a defense mechanism.[60]

Mosquito nets and
bedclothes

Mosquito nets help keep mosquitoes away from people and greatly
reduce the infection and transmission of malaria. The nets are not
a perfect barrier and they are often treated with an insecticide
designed to kill the mosquito before it has time to search for a
way past the net. Insecticide-treated nets (ITN) are estimated to
be twice as effective as untreated nets and offer greater than 70%
protection compared with no net.[61].
Although ITN are proven to be very effective against malaria, less
than 2% of children in urban areas in Sub-Saharan Africa are
protected by ITNs. Since the Anopheles mosquitoes feed at night, the
preferred method is to hang a large "bed net" above the center of a
bed such that it drapes down and covers the bed completely.

The distribution of mosquito nets impregnated with insecticides
such as permethrin or
deltamethrin has been shown to be an extremely effective method of
malaria prevention, and it is also one of the most cost-effective
methods of prevention. These nets can often be obtained for around
$2.50–$3.50 (2–3 euros) from the United Nations, the World Health
Organization (WHO), and others. ITNs have been shown to be the most
cost-effective prevention method against malaria and are part of
WHO’s Millennium Development Goals (MDGs).

For maximum effectiveness, the nets should be re-impregnated
with insecticide every six months. This process poses a significant
logistical problem in rural areas. New technologies like Olyset or
DawaPlus allow for production of long-lasting insecticidal mosquito
nets (LLINs), which release insecticide for approximately
5 years,[62] and
cost about US$5.50. ITNs protect people sleeping under the net and
simultaneously kill mosquitoes that contact the net. Some
protection is also provided to others by this method, including
people sleeping in the same room but not under the net.

While distributing mosquito nets is a major component of malaria
prevention, community education and awareness on the dangers of
malaria are associated with distribution campaigns to make sure
people who receive a net know how to use it. "Hang Up" campaigns
such as the ones conducted by volunteers of the International
Red Cross and Red Crescent Movement consist of visiting
households that received a net at the end of the campaign or just
before the rainy season, ensuring that the net is being used
properly and that the people most vulnerable to malaria, such as
young children and the elderly, sleep under it. A study conducted
by the CDC in Sierra Leone showed a
22 percent increase in net utilization following a personal visit
from a volunteer living in the same community promoting net usage.
A study in Togo showed similar
improvements.[63]

Mosquito nets are often unaffordable to people in developing
countries, especially for those most at risk. Only 1 out of 20
people in Africa own a bed net. Nets are also often distributed
though vaccine campaigns using voucher subsidies, such as the
measles campaign for children. A study among Afghan refugees
in Pakistan found that treating top-sheets and chaddars (head
coverings) with permethrin has similar effectiveness to using a
treated net, but is much cheaper.[64]
Another alternative approach uses spores of the fungusBeauveria bassiana, sprayed on
walls and bed nets, to kill mosquitoes. While some mosquitoes have
developed resistance to chemicals, they have not been found to
develop a resistance to fungal infections.[65]

Vaccination

Immunity (or, more accurately, tolerance) does occur naturally,
but only in response to repeated infection with multiple strains of
malaria.[66]

Vaccines for
malaria are under development, with no completely effective vaccine
yet available. The first promising studies demonstrating the
potential for a malaria vaccine were performed in 1967 by
immunizing mice with live, radiation-attenuatedsporozoites, providing
protection to about 60% of the mice upon subsequent injection with
normal, viable sporozoites.[67]
Since the 1970s, there has been a considerable effort to develop
similar vaccination strategies within humans. It was determined
that an individual can be protected from a P. falciparum
infection if they receive over 1,000 bites from infected,
irradiated mosquitoes.[68]

It has been generally accepted that it is impractical to provide
at-risk individuals with this vaccination strategy, but that has
been recently challenged with work being done by Dr. Stephen
Hoffman, one of the key researchers who originally sequenced the
genome of Plasmodium falciparum. His
work most recently has revolved around solving the logistical
problem of isolating and preparing the parasites equivalent to 1000
irradiated mosquitoes for mass storage and inoculation of human
beings. The company has recently received several multi-million
dollar grants from the Bill & Melinda
Gates Foundation and the U.S. government to begin early
clinical studies in 2007 and 2008.[69]
The Seattle Biomedical Research Institute (SBRI), funded by the
Malaria Vaccine Initiative, assures potential volunteers that "the
[2009] clinical trials won't be a life-threatening experience.
While many volunteers [in Seattle] will actually contract malaria,
the cloned strain used in the experiments can be quickly cured, and
does not cause a recurring form of the disease." "Some participants
will get experimental drugs or vaccines, while others will get
placebo."[70]

Instead, much work has been performed to try and understand the
immunological
processes that provide protection after immunization with
irradiated sporozoites. After the mouse vaccination study in
1967,[67]
it was hypothesized that the injected sporozoites themselves were
being recognized by the immune system, which was in turn creating
antibodies against the
parasite. It was determined that the immune system was creating
antibodies against the circumsporozoite protein (CSP) which coated
the sporozoite.[71]
Moreover, antibodies against CSP prevented the sporozoite from
invading hepatocytes.[72] CSP
was therefore chosen as the most promising protein on which to
develop a vaccine against the malaria sporozoite. It is for these
historical reasons that vaccines based on CSP are the most numerous
of all malaria vaccines.

Presently, there is a huge variety of vaccine candidates on the
table. Pre-erythrocytic vaccines (vaccines that target the parasite
before it reaches the blood), in particular vaccines based on CSP,
make up the largest group of research for the malaria vaccine.
Other vaccine candidates include: those that seek to induce
immunity to the blood stages of the infection; those that seek to
avoid more severe pathologies of malaria by preventing adherence of
the parasite to blood venules and placenta; and transmission-blocking vaccines
that would stop the development of the parasite in the mosquito
right after the mosquito has taken a bloodmeal from an infected
person.[73]
It is hoped that the knowledge of the P. falciparumgenome, the sequencing of which
was completed in 2002[74], will
provide targets for new drugs or vaccines.[75]

The first vaccine developed that has undergone field trials, is
the SPf66, developed by Manuel Elkin Patarroyo in 1987.
It presents a combination of antigens from the sporozoite (using CS
repeats) and merozoite parasites. During phase I trials a 75%
efficacy rate was demonstrated and the vaccine appeared to be well
tolerated by subjects and immunogenic. The phase IIb and III trials
were less promising, with the efficacy falling to between 38.8% and
60.2%. A trial was carried out in Tanzania in 1993 demonstrating
the efficacy to be 31% after a years follow up, however the most
recent (though controversial) study in The Gambia did not show any
effect. Despite the relatively long trial periods and the number of
studies carried out, it is still not known how the SPf66 vaccine
confers immunity; it therefore remains an unlikely solution to
malaria. The CSP was the next vaccine developed that initially
appeared promising enough to undergo trials. It is also based on
the circumsporoziote protein, but additionally has the recombinant
(Asn-Ala-Pro15Asn-Val-Asp-Pro)2-Leu-Arg(R32LR) protein covalently
bound to a purified Pseudomonas aeruginosa
toxin (A9). However at an early stage a complete lack of protective
immunity was demonstrated in those inoculated. The study group used
in Kenya had an 82% incidence of parasitaemia whilst the control
group only had an 89% incidence. The vaccine intended to cause an
increased T-lymphocyte response in those exposed, this was also not
observed.

The efficacy of Patarroyo's vaccine has been disputed with some
US scientists concluding in The Lancet (1997) that "the vaccine was not
effective and should be dropped" while the Colombian accused them
of "arrogance" putting down their assertions to the fact that he
came from a developing country.

The RTS,S/AS02A vaccine is the candidate furthest along in
vaccine trials. It is being developed by a partnership between the
PATH Malaria Vaccine Initiative (a grantee of the Gates
Foundation), the pharmaceutical
company, GlaxoSmithKline, and the Walter Reed
Army Institute of Research[76] In
the vaccine, a portion of CSP has been fused to the immunogenic "S antigen" of the hepatitis B virus; this
recombinant protein
is injected alongside the potent AS02A adjuvant.[73]
In October 2004, the RTS,S/AS02A researchers announced results of a
Phase IIb
trial, indicating the vaccine reduced infection risk by
approximately 30% and severity of infection by over 50%. The study
looked at over 2,000 Mozambican children.[77] More
recent testing of the RTS,S/AS02A vaccine has focused on the safety
and efficacy of administering it earlier in infancy: In October
2007, the researchers announced results of a phase I/IIb trial
conducted on 214 Mozambican infants between the ages of 10 and 18
months in which the full three-dose course of the vaccine led to a
62% reduction of infection with no serious side-effects save some
pain at the point of injection.[78]
Further research will delay this vaccine from commercial release
until around 2011.[79]

Other
methods

Education in recognizing the symptoms of malaria has reduced the
number of cases in some areas of the developing world by as much as
20%. Recognizing the disease in the early stages can also stop the
disease from becoming a killer. Education can also inform people to
cover over areas of stagnant, still water e.g. Water Tanks which
are ideal breeding grounds for the parasite and mosquito, thus
cutting down the risk of the transmission between people. This is
most put in practice in urban areas where there are large centers
of population in a confined space and transmission would be most
likely in these areas.

The Malaria Control Project is
currently using downtime computing power donated by individual
volunteers around the world (see Volunteer computing and BOINC) to
simulate models of the health effects and transmission dynamics in
order to find the best method or combination of methods for malaria
control. This modeling is extremely computer intensive due to the
simulations of large human populations with a vast range of
parameters related to biological and social factors that influence
the spread of the disease. It is expected to take a few months
using volunteered computing power compared to the 40 years it would
have taken with the current resources available to the scientists
who developed the program.[80]

An example of the importance of computer modeling in planning
malaria eradication programs
is shown in the paper by Águas and others. They showed that
eradication of malaria is crucially dependent on finding and
treating the large number of people in endemic areas with
asymptomatic malaria, who act as a reservoir for infection.[81] The
malaria parasites do not affect animal species and therefore
eradication of the disease from the human population would be
expected to be effective.

Treatment

Active malaria infection with P. falciparum is a medical
emergency requiring hospitalization. Infection with P.
vivax, P. ovale or P. malariae can often be
treated on an outpatient basis. Treatment of malaria involves
supportive measures as well as specific antimalarial drugs. Most antimalarial drugs
are produced industrially and are sold at pharmacies. However, as
the cost of such medicins are often too high for most people in the
developing world, some herbal remedies (such as Artemisia annua
tea[82] have
also been developed, and have gained support from international
organisations as Médicins Sans Frontières. When properly treated,
someone with malaria can expect a complete recovery.[83]

Counterfeit
drugs

Sophisticated counterfeits have
been found in several Asian countries such as Cambodia,[84]China,[85]Indonesia, Laos, Thailand, Vietnam and are an important cause of avoidable
death in those countries.[86]WHO have said that
studies indicate that up to 40% of artesunate based malaria medications are
counterfeit, especially in the Greater Mekong region and have established a rapid alert
system to enable information about counterfeit drugs to be rapidly
reported to the relevant authorities in participating
countries.[87] There
is no reliable way for doctors or lay people to detect counterfeit
drugs without help from a laboratory. Companies are attempting to
combat the persistence of counterfeit drugs by using new technology
to provide security from source to distribution.

Malaria causes about 250 million cases of fever and
approximately one million deaths annually.[89]
The vast majority of cases occur in children under 5 years old;[90]
pregnant women are also especially vulnerable. Despite efforts to
reduce transmission and increase treatment, there has been little
change in which areas are at risk of this disease since 1992.[91]
Indeed, if the prevalence of malaria stays on its present upwards
course, the death rate could double in the next twenty years.[92]
Precise statistics are unknown because many cases occur in rural
areas where people do not have access to hospitals or the means to
afford health care. As a consequence, the majority of cases are
undocumented.[92]

Although co-infection with HIV and malaria does cause increased
mortality, this is less of a problem than with HIV/tuberculosis
co-infection, due to the two diseases usually attacking different
age-ranges, with malaria being most common in the young and active
tuberculosis most common in the old.[93]
Although HIV/malaria co-infection produces less severe symptoms
than the interaction between HIV and TB, HIV and malaria do
contribute to each other's spread. This effect comes from malaria
increasing viral load
and HIV infection increasing a person's susceptibility to malaria
infection.[94]

Malaria is presently endemic in a broad band around the equator,
in areas of the Americas,
many parts of Asia, and much of Africa; however, it is in
sub-Saharan Africa where 85– 90% of malaria fatalities occur.[95] The
geographic distribution of malaria within large regions is complex,
and malaria-afflicted and malaria-free areas are often found close
to each other.[96]
In drier areas, outbreaks of malaria can be predicted with
reasonable accuracy by mapping rainfall.[97]
Malaria is more common in rural areas than in cities; this is in
contrast to dengue
fever where urban areas present the greater risk.[98] For
example, the cities of Vietnam, Laos
and Cambodia are
essentially malaria-free, but the disease is present in many rural
regions.[99] By
contrast, in Africa malaria is present in both rural and urban
areas, though the risk is lower in the larger cities.[100] The
global endemic levels of malaria have
not been mapped since the 1960s. However, the Wellcome Trust,
UK, has funded the Malaria Atlas Project[101] to
rectify this, providing a more contemporary and robust means with
which to assess current and future malaria disease
burden.

History

Malaria has infected humans for over 50,000 years, and
Plasmodium may have been a human pathogen for the entire history of the
species.[102]
Close relatives of the human malaria parasites remain common in
chimpanzees.[103]
References to the unique periodic fevers of malaria are found
throughout recorded history, beginning in 2700 BC in China.[104] The
term malaria originates from MedievalItalian: mala aria—"bad air"; and the disease was
formerly called ague or marsh fever due to its
association with swamps and marshland.[105]
Malaria was once common in most of Europe and North America, where it is no longer endemic[106],
though imported cases do occur.

However, it was Britain's Sir Ronald Ross working in the Presidency
General Hospital in Calcutta who finally proved in 1898 that
malaria is transmitted by mosquitoes. He did this by showing that
certain mosquito species transmit malaria to birds and isolating
malaria parasites from the salivary glands of mosquitoes that had
fed on infected birds.[112] For
this work Ross received the 1902 Nobel Prize in Medicine. After
resigning from the Indian Medical Service, Ross worked at the
newly-established Liverpool School of
Tropical Medicine and directed malaria-control efforts in Egypt, Panama, Greece and Mauritius.[113] The
findings of Finlay and Ross were later confirmed by a medical board
headed by Walter
Reed in 1900, and its recommendations implemented by William C.
Gorgas in
the health measures undertaken during construction of the Panama Canal. This
public-health work saved the lives of thousands of workers and
helped develop the methods used in future public-health campaigns
against this disease.

The first effective treatment for malaria came from the bark of
cinchona tree, which
contains quinine. This tree
grows on the slopes of the Andes, mainly in Peru. A tincture made of this natural product was
used by the inhabitants of Peru to
control malaria, and the Jesuits introduced this practice to Europe
during the 1640s, where it was rapidly accepted.[114]
However, it was not until 1820 that the active ingredient, quinine,
was extracted from the bark, isolated and named by the French
chemists Pierre Joseph Pelletier and Joseph Bienaimé Caventou.[115]

In the early 20th century, before antibiotics became
available, Julius Wagner-Jauregg discovered
that patients with syphilis could be treated by intentionally
infecting them with malaria; the resulting fever would kill the
syphilis spirochetes, and quinine would then be administered to control
the malaria. Although some patients died from malaria, this was
considered preferable to the almost-certain death from
syphilis.[116]

The first successful continuous malaria culture was established in 1976
by William Trager and James B. Jensen, which facilitated research
into the molecular biology of the parasite and the development of
new drugs substantially.[117][118]

Although the blood stage and mosquito stages of the malaria life
cycle were identified in the 19th and early 20th centuries, it was
not until the 1980s that the latent liver form of the parasite was
observed.[119][120] The
discovery of this latent form of the parasite finally explained why
people could appear to be cured of malaria but still relapse years
after the parasite had disappeared from their bloodstreams.

Sickle-cell
disease

The most-studied influence of the malaria parasite upon the
human genome is a hereditary blood disease, sickle-cell
disease. The sickle-cell trait causes disease, but even those
only partially affected by sickle-cell have substantial protection
against malaria.

In sickle-cell disease, there is a mutation in the HBB
gene, which encodes the beta-globin subunit of haemoglobin. The normal allele encodes a glutamate at position six of the
beta-globin protein, whereas the sickle-cell allele encodes a valine. This change from a
hydrophilic to a hydrophobic amino acid encourages binding between
haemoglobin molecules, with polymerization of haemoglobin deforming
red blood cells into a "sickle" shape. Such deformed cells are
cleared rapidly from the blood, mainly in the spleen, for
destruction and recycling.

In the merozoite stage of its life cycle, the malaria parasite
lives inside red blood cells, and its metabolism changes the
internal chemistry of the red blood cell. Infected cells normally
survive until the parasite reproduces, but, if the red cell
contains a mixture of sickle and normal haemoglobin, it is likely
to become deformed and be destroyed before the daughter parasites
emerge. Thus, individuals heterozygous for the
mutated allele, known as sickle-cell trait, may have a low and
usually-unimportant level of anaemia, but also have a greatly reduced
chance of serious malaria infection. This is a classic example of
heterozygote advantage.

Individuals homozygous for the mutation have full
sickle-cell disease and in traditional societies rarely live beyond
adolescence. However, in populations where malaria is endemic, the frequency of sickle-cell genes is around
10%. The existence of four haplotypes of sickle-type hemoglobin suggests
that this mutation has emerged independently at least four times
in malaria-endemic areas, further demonstrating its evolutionary
advantage in such affected regions. There are also other mutations
of the HBB gene that produce haemoglobin molecules capable of
conferring similar resistance to malaria infection. These mutations
produce haemoglobin types HbE and HbC, which are common in Southeast Asia
and Western Africa, respectively.

Thalassaemias

Another well-documented set of mutations found in the human
genome associated with malaria are those involved in causing blood
disorders known as thalassaemias. Studies in Sardinia and Papua New
Guinea have found that the gene frequency of β-thalassaemias is
related to the level of malarial endemicity in a given population.
A study on more than 500 children in Liberia found that those with β-thalassaemia
had a 50% decreased chance of getting clinical malaria. Similar
studies have found links between gene frequency and malaria
endemicity in the α+ form of α-thalassaemia. Presumably these genes
have also been selected in the course of human
evolution.

Duffy
antigens

The Duffy antigens are antigens expressed on red
blood cells and other cells in the body acting as a chemokine receptor. The
expression of Duffy antigens on blood cells is encoded by Fy genes
(Fya, Fyb, Fyc etc.). Plasmodium vivax malaria uses the
Duffy antigen to enter blood cells. However, it is possible to
express no Duffy antigen on red blood cells (Fy-/Fy-). This genotype confers complete
resistance to P. vivax infection. The genotype is very
rare in European, Asian and American populations, but is found in
almost all of the indigenous population of West and Central
Africa.[123]
This is thought to be due to very high exposure to P.
vivax in Africa in the
last few thousand years.

HLA and
interleukin-4

HLA-B53 is associated with low
risk of severe malaria. This MHC class I molecule
presents liver stage and sporozoiteantigens to T-Cells.
Interleukin-4, encoded by IL4, is produced by activated T cells and
promotes proliferation and differentiation of antibody-producing B
cells. A study of the Fulani of Burkina Faso, who have both fewer
malaria attacks and higher levels of antimalarial antibodies than
do neighboring ethnic groups, found that the IL4-524 T allele was
associated with elevated antibody levels against malaria antigens,
which raises the possibility that this might be a factor in
increased resistance to malaria.[124]

Resistance in South Asia

The lowest Himalayan Foothills and Inner Terai or Doon
Valleys of Nepal and India are highly malarial due to a
warm climate and marshes sustained during the dry season by
groundwater percolating down from the higher hills. Malarial
forests were intentionally maintained by the rulers of Nepal as a
defensive measure. Humans attempting to live in this zone suffered
much higher mortality than at higher elevations or below on the
drier Gangetic Plain, however the Tharu people had
lived in this zone long enough to evolve resistance via multiple
genes. Endogamy along
caste and ethnic lines appear to have confined these to the Tharu
community. Otherwise these genes probably would have become nearly
universal in South Asia and beyond because of their considerable
survival value and the apparent lack of negative effects comparable
to Sickle Cell Anemia.

Society and
culture

Malaria is not just a disease commonly associated with poverty
but also a cause of poverty and a major hindrance to economic
development. Tropical regions are affected most, however
malaria’s furthest extent reaches into some temperate zones with
extreme seasonal changes. The disease has been associated with
major negative economic effects on regions where it is widespread.
During the late 19th and early 20th centuries, it was a major
factor in the slow economic development of the American southern
states.[125].
A comparison of average per capita GDP in 1995, adjusted for parity of purchasing power,
between countries with malaria and countries without malaria gives
a fivefold difference ($1,526 USD versus $8,268 USD). In countries
where malaria is common, average per capita GDP has risen (between
1965 and 1990) only 0.4% per year, compared to 2.4% per year in
other countries.[126]
Poverty is both cause and effect, however, since the poor do not
have the financial capacities to prevent or treat the disease. The
lowest income group in Malawi carries (1994) the burden of having
32% of their annual income used on this disease compared with the
4% of household incomes from low-to-high groups.[127] In
its entirety, the economic impact of malaria has been estimated to
cost Africa $12 billion USD every year. The economic impact
includes costs of health care, working days lost due to sickness,
days lost in education, decreased productivity due to brain damage
from cerebral malaria, and loss of investment and tourism.[90]
In some countries with a heavy malaria burden, the disease may
account for as much as 40% of public health expenditure, 30-50% of
inpatient admissions, and up to 50% of outpatient visits.[128]

From Wikitravel

Contents

Malaria is a serious and sometimes fatal tropical
disease. Four kinds of malaria parasites can infect humans:
Plasmodium falciparum, P. vivax, P. ovale, and P. malariae;
infection with P. falciparum, if not promptly and correctly
treated, can be fatal in as little as one or two days.

Competent advice from an up-to-date source of
information, such as the tropical diseases department of a major
hospital, is essential.

Transmission

According to the CDC, Malaria is
transmitted in large areas of Central and South America, the island
of Hispaniola (includes Haiti and the Dominican Republic), Africa,
Asia (including the Indian subcontinent, Southeast Asia and the
Middle East), and a few areas of Eastern Europe and the South
Pacific.

In general, the risk of contracting malaria is higher in rural
areas and lower in urban areas. Often there is also a correlation
to the mosquito population, with the rainy season creating stagnant
pools of water where mosquitoes can breed.

Symptoms

Symptoms of malaria mimic common flu, with an infected person
suffering fever, headache, and vomiting usually within 10 to 15
days after the mosquito bite. This means that you may become sick
when you're already back at home, so be aware of that.

Malaria is life-threatening, and requires
immediate treatment. No vaccine is currently
available, but methods of prevention include avoiding mosquito bites and
preventative drugs (prophylaxis). Note that some drugs are not
effective for all areas. If a person who has visited a malaria risk
zone contracts a fever within one year, their
physician should be informed of the possibility of malaria. Less
serious forms (such as P. vivax) can mimic symptoms of the
flu. Physicians who rarely, if ever, examine malaria patients may
need to be reminded of this fact. The standard laboratory test for
malaria is a thick and thin blood smear on a glass slide viewed
under the microscope. Self-test kits are highly unreliable.

Prophylaxis

Any malaria prophylaxis must be taken before, during, and
(especially) after traveling to a malaria-risk zone. Anti-malarial
drugs are highly effective in preventing malaria. As with all
drugs, anti-malarials may cause side-effects, and their
effectiveness may be compromised by various factors (e.g.
resistance); a specialist doctor should be consulted beforehand.
Seldom will malaria be the sole health concern, and the physician
will need to assess all the health risks the traveler will face.
Most often a general practitioner cannot prescribe medications or
give vaccinations for third-world travel. Prophylaxis is cheaper
and more up to date in countries with Malaria. However, one must
obtain it from a reliable chemist, usually in a high-end or tourist
area. Sometimes, the pills might be placebos, there have been many
cases of this of pills coming from China. gu

Pregnant women should be especially careful, as some
anti-malarials must not be taken during pregnancy, and malaria
during pregnancy is usually more severe and is always considered to
be a serious emergency. As with most prophylaxis, anti-malarials
are not 100% effective; however studies have shown that when taken
as directed, the most common drugs (e.g. doxycycline, Malarone) are
~98%~99% effective. The choice of a malaria prophylaxis should be
made carefully with one's physician, taking into account drug
resistance in the traveler's destination; possible side effects,
interactions, and contraindications; and finally the preferred
frequency per dose (daily, weekly, etc.)

Even before considering prophylactic medications, there are
important anti-insect measures that should be used. Avoiding
mosquito bites (i.e. using DEET, screens, and proper bed netting)
when mosquitoes are obviously present is important as well. For
those sensitive to DEET, or dislike its smell, repellents
containing Picaridin (e.g. Cutter Advanced) are available
in limited areas. This has been shown to be as effective as DEET,
and has almost no odor.

The most common anti-malarials include:

Doxycycline is highly effective and can be
very inexpensive. Possible disadvantages include increased sun
sensitivity (sunburning easier), and nausea and stomach pain; some
sources caution that it may reduce the effectiveness of birth
control pills.

Lariam (mefloquine), or it's generic
Mefliam, is highly effective, has a simple weekly
dose and can be taken for extended periods. It does have a number
of contra-indications and must be prescribed by a doctor, and has
also been known to have very rare but severe neurological side
effects. More common side effects include nausea,stomach cramps and
lucid dreams. Not to be used if you plan on scuba diving or high
altitude climbing. Your doctor may advise that you start using it
several weeks before leaving, in order to check for possible side
effects. There are resistant mosquitoes in Southeast Asia, and West
and East Africa. Find out the latest information on this drug from
a professional before purchase.

Malarone (atovaquone + proguanil) is highly
effective, has a very low incidence of side effects, and only needs
to be taken for one week after leaving the risk area; however it is
expensive.

Chloroquine (Daramal / Nivaquine / Promal)
in combination with proguanil (Paludrine) may
sometimes be recommended, and is generally well tolerated. Problems
include people having difficulty adhering to the prescribed regime
due to its complexity, and widespread resistance.

There has been some debate recently over whether pre-travel
malaria prophylaxis is being started early enough. For example,
mefloquine is normally taken one week prior to travel. Some feel
this is inadequate if the person is unfortunate enough to be
exposed to malaria shortly upon arrival. Those who have concerns
may wish to discuss with their physician the option of doubling the
time period (not the dosage) that their malaria prophylaxis will be
taken prior to travel. In addition to providing better protection,
there will be more time to switch to another anti-malaria
medication, if necessary.

Aspirin must never be taken as an antipyretic (fever reducer)
when malaria or dengue fever is a possibility. (Continuing daily
low-dose 81 mg aspirin therapy during and after third-world travel
should be discussed with your physician.) Acetaminophen
(paracetamol) and ibuprofen are considered safe alternatives
provided all of their precautions are observed. Malaria, dengue
fever, and typhoid fever all tend to have somewhat similar symptoms
at first and should not be self-diagnosed.

Travel

Travel to rural areas always involves more potential exposure to
malaria than in the larger cities. (This is in contrast to dengue
fever where cities present the greater risk.) For example, the
capital cities of the Philippines, Thailand and Sri Lanka are
essentially malaria-free. However, malaria is present in many other
places (especially rural areas) of these countries. By contrast, in
West Africa, Ghana and Nigeria have malaria throughout the entire
country. However, the risk will always be lower in the larger
cities. Travelers should never assume that their choice of malaria
prophylaxis is available in the country that they will be visiting.
Many third-world countries stock only chloroquine and possibly
doxycycline. Quinine might also be available, but is not
recommended as a prophylactic anti-malarial.

From Wikiversity

Malaria is a vector-borne infectious disease that is widespread
in tropical and subtropical regions, including parts of the
Americas, Asia, and Africa. Each year, it causes disease in
approximately 650 million people and kills between one and three
million, most of them young children in Sub-Saharan Africa. Malaria
is commonly-associated with poverty, but is also a cause of poverty
and a major hindrance to economic development.

Malaria is one of the most common infectious diseases and an
enormous public-health problem. The disease is caused by protozoan
parasites of the genus Plasmodium. The most serious forms of the
disease are caused by Plasmodium falciparum and Plasmodium vivax,
but other related species (Plasmodium ovale, Plasmodium malariae,
and sometimes Plasmodium knowlesi) can also infect humans. This
group of human-pathogenic Plasmodium species is usually referred to
as malaria parasites.

Malaria parasites are transmitted by female Anopheles
mosquitoes. The parasites multiply within red blood cells, causing
symptoms that include symptoms of anemia (light headedness,
shortness of breath, tachycardia etc.), as well as other general
symptoms such as fever, chills, nausea, flu-like illness, and in
severe cases, coma and death. Malaria transmission can be reduced
by preventing mosquito bites with mosquito nets and insect
repellents, or by mosquito control by spraying insecticides inside
houses and draining standing water where mosquitoes lay their
eggs.

No vaccine is currently available for malaria; preventative
drugs must be taken continuously to reduce the risk of infection.
These prophylactic drug treatments are often too expensive for most
people living in endemic areas. Most adults from endemic areas have
a degree of long-term recurrent infection and also of partial
resistance; the resistance reduces with time and such adults may
become susceptible to severe malaria if they have spent a
significant amount of time in non-endemic areas. They are strongly
recommended to take full precautions if they return to an endemic
area. Malaria infections are treated through the use of
antimalarial drugs, such as quinine or artemisinin derivatives,
although drug resistance is increasingly common.

Contents

Causes

A Plasmodium sporozoite traverses the cytoplasm of a
mosquito midgut epithelial cell in this false-color electron
micrograph.

Malaria
parasites

Malaria is caused by protozoan parasites of the genus
Plasmodium (phylum Apicomplexa). In humans malaria is
caused by P. falciparum, P. malariae, P.
ovale, and P. vivax. However, P. falciparum
is the most important cause of disease and responsible for about
80% of infections and 90% of deaths.[1] Parasitic
Plasmodium species also infect birds, reptiles, monkeys,
chimpanzees and rodents.[2] There have been documented human
infections with several simian species of malaria, namely P.
knowlesi, P. inui, P. cynomolgi[3], P. simiovale, P.
brazilianum, P. schwetzi and P. simium;
however these are mostly of limited public health importance.
Although avian malaria can kill chickens and turkeys, this disease
does not cause serious economic losses to poultry farmers.[4] However, since being accidentally
introduced by humans it has decimated the endemic birds of Hawaii,
which evolved in its absence and lack any resistance to it.[5]

Pathogenesis

Malaria in humans develops via two phases: an exoerythrocytic
(hepatic) and an erythrocytic phase. When an infected mosquito
pierces a person's skin to take a blood meal, sporozoites in the
mosquito's saliva enter the bloodstream and migrate to the liver.
Within 30 minutes of being introduced into the human host, they
infect hepatocytes, multiplying asexually and asymptomatically for
a period of 6–15 days. During this so-called dormant time in the
liver, the sporozoites are often referred to as hypnozoites. Once
in the liver these organisms differentiate to yield thousands of
merozoites which, following rupture of their host cells, escape
into the blood and infect red blood cells, thus beginning the
erythrocytic stage of the life cycle.[6] The parasite
escapes from the liver undetected by wrapping itself in the cell
membrane of the infected host liver cell.[7]

Within the red blood cells the parasites multiply further, again
asexually, periodically breaking out of their hosts to invade fresh
red blood cells. Several such amplification cycles occur. Thus,
classical descriptions of waves of fever arise from simultaneous
waves of merozoites escaping and infecting red blood cells.

Some P. vivax and P. ovale sporozoites do not
immediately develop into exoerythrocytic-phase merozoites, but
instead produce hypnozoites that remain dormant for periods ranging
from several months (6–12 months is typical) to as long as three
years. After a period of dormancy, they reactivate and produce
merozoites. Hypnozoites are responsible for long incubation and
late relapses in these two species of malaria.[8]

The parasite is relatively protected from attack by the body's
immune system
because for most of its human life cycle it resides within the
liver and blood cells and is relatively invisible to immune
surveillance. However, circulating infected blood cells are
destroyed in the spleen. To avoid this fate, the P.
falciparum parasite displays adhesive proteins on the surface
of the infected blood cells, causing the blood cells to stick to
the walls of small blood vessels, thereby sequestering the parasite
from passage through the general circulation and the spleen.[9] This "stickiness" is the
main factor giving rise to hemorrhagic complications of malaria.
High endothelial venules (the smallest branches of the circulatory
system) can be blocked by the attachment of masses of these
infected red blood cells. The blockage of these vessels causes
symptoms such as in placental and cerebral malaria. In cerebral
malaria the sequestrated red blood cells can breach the blood brain
barrier possibly leading to coma.[10]

Although the red blood cell surface adhesive proteins (called
PfEMP1, for Plasmodium falciparum erythrocyte membrane
protein 1) are exposed to the immune system they do not serve as
good immune targets because of their extreme diversity; there are
at least 60 variations of the protein within a single parasite and
perhaps limitless versions within parasite populations.[9] Like a thief changing
disguises or a spy with multiple passports, the parasite switches
between a broad repertoire of PfEMP1 surface proteins, thus staying
one step ahead of the pursuing immune system.

Some merozoites turn into male and female gametocytes. If a
mosquito pierces the skin of an infected person, it potentially
picks up gametocytes within the blood. Fertilization and sexual
recombination of the parasite occurs in the mosquito's gut, thereby
defining the mosquito as the definitive host of the disease. New
sporozoites develop and travel to the mosquito's salivary gland,
completing the cycle. Pregnant women are especially attractive to
the mosquitoes,[11] and malaria in pregnant women
is an important cause of stillbirths, infant mortality and low
birth weight.[12]

German

Noun

Synonyms

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[[File:|thumb|230px|Electron micrograph of a malaria sporozoite]]

Malaria is an infectious disease. It is caused by parasites. People catch malaria when the parasite enters the blood. A parasite is an organism that lives off of another organism called a host. A parasite takes from the host organism, but does not help it. Instead, it usually harms the host.

The parasite that causes malaria is a protozoan called Plasmodium. Protozoa are organisms with only one cell, but they are not bacteria. Bacteria are smaller and simpler than protozoa.

There are several species (kinds) of Plasmodium that cause malaria in people:

Plasmodium falciparum

Plasmodium knowesli

Plasmodium malariae

Plasmodium ovale

Plasmodium semiovale

Plasmodium vivax

P. vivax and P. falciparum cause the most malaria in people. Falciparum malaria is the worst kind, and kills the most people.

People usually get malaria from the Anopheles mosquitoes. The Plasmodium goes into people by mosquitoes bites. The Plasmodium is in the mosquito's saliva. (Saliva is moisture, or spit, made in the mouth.) The mosquito's saliva carries the Plasmodium into the person. The person is then infected with Plasmodium. This makes the person have the disease malaria.

The kind of mosquito that carries malaria is the anopheles mosquito. Only the female mosquito gives people malaria, because only the female mosquito bites.

Some people do not get malaria from mosquitoes. A baby can get it while inside its mother. This is called maternal-fetal transmission. People can also get malaria from a blood transfusion. This is when someone gives blood to another person. Another way people can catch malaria is by using a needle that someone with the disease used before them.

How Plasmodium lives in people

When Plasmodium enters the blood, they are then called sporozoites. Sporozoites go to the liver, where they make many more sporozoites. Then they change into a different form of Plasmodium. This form is the merozoite. The merozoites go into the red blood cells, then they make many more merozoites.

The merozoites break out of the red blood cells again and again. When they do this, the person gets very sick, and shows symptoms of malaria. This happens every few days, and is called a paroxysm.

P. vivax and P. ovale can live in the liver for a long time. A person can look well, but still have the Plasmodium in the liver. This is called a dormant phase. Weeks or months later, the Plasmodium can leave the liver to the blood, and the person will get sick again.

P. falciparum is the most dangerous type of malaria. It makes people sicker than those with other types of malaria, because there are more of them in the blood. Also, with falciparum malaria, the red blood cells are sticky. This makes the red blood cells block blood vessels. If blood vessels are blocked, this can hurt what the blood vessel brings blood to, and can hurt people's organs.

Who is affected by malaria

Pregnant women and children are hurt most by malaria. When they get malaria, they get sicker.

40% of people live in a place where there is malaria. Malaria is in these places:

Every year, 300 to 700 million people get malaria. It kills 1 million to 2 million people every year. The biggest problem is in Africa. 90% of the people who die from malaria are there. Most of the people who die from malaria are children. In Africa, 20% of children under five die from malaria. Even if children do not die, many have brain damage.

Most of these deaths could be stopped with medicine or with ways to stop mosquitoes. UNICEF says: the medicine that costs the most for malaria is only $2.40 to help one adult. But many of the places malaria may be found are in poor countries. These countries do not have enough money to stop the mosquitoes, or to give people medicine.

Symptoms of malaria

Symptoms are changes in someone's body that are signs for a disease. Most people who get malaria get symptoms 10–30 days after they get infected (the Plasmodium gets in their blood.) But some people can get symptoms after only a week, and some may be infected with malaria and not have symptoms for a year.

The most common symptom of malaria is fever, when the body temperature is high. The fever from malaria usually comes very suddenly. The people who have Malaria often feel like they had influenza.

How doctors tell if someone has malaria

In places where malaria is, there may not be good medical care. People may diagnose malaria just by people having symptoms. Diagnose means to learn if a person has a disease. Doctors diagnose people sometimes just by symptoms. This is called a clinical diagnosis. Doctors also use tests to see if people have a disease.

If a person has symptoms and is in a place where there is malaria, they might have malaria. To see if they have malaria, doctors may do a blood test. This test is called a Giemsa blood smear. Blood is put on a slide which is a thin piece of glass. The Giemsa stain is put on the slide. This stain helps doctors see the malaria. Then they look at the slide under a microscope. The Plasmodium is seen in the red blood cells.

Sometimes the blood smear will not show Plasmodium even if the person has malaria. This can be because the stain was not good. It can also be because the microscope was not good. Or it can be because the person looking in the microscope did not know what Plasmodium look like. But often it is because the number of malaria parasites present in the blood is so low that they are not present in the section of the blood that was looked at.

There are other tests to diagnose malaria. These are more expensive. People do not use them as much. Sometimes people test to see if the Plasmodium is resistant to medicines to treat malaria. Resistance means the medicine cannot hurt the Plasmodium. This means that taking the medicine will not cure someone with malaria, because it will not kill the Plasmodium.

How to treat malaria

People with different kinds of malaria need different medicines. The medicine that works for one kind of malaria may not for another kind. So it is very important to know which species of Plasmodium the person has.

If the species is not known, the person should be given medicine and care like they have falciparum malaria - the worst kind.

It is also important to know where the person got malaria. Plasmodium in some places are resistant to some medicines. So the medicines to treat malaria in Africa are different from the medicines to treat malaria from South America.

It is important for doctors to learn about malaria treatment. Resistance to medicines changes. Places where there was no resistance can get resistant malaria. So doctors need to know when this changes. If a doctor treats a person with malaria, he should know what places in the world have resistant malaria. If he has not treated a person in a long time, he should check before treating people.

Treatment of malaria other than falciparum

Everywhere except New Guinea, the treatment is the same. In New Guinea most P. vivax is resistant to chloroquine. It can be treated with quinine, but this medicine can make people sick. Everywhere else, non-falciparum malaria is treated with chloroquine.

Chloroquine kills the Plasmodium in the blood. But the Plasmodium in the liver is not killed by chloroquine. P. vivax and P. ovale both stay in the liver a long time. This is the dormant phase. Another medicine must be given with chloroquine for P. vivax and P. ovale. This is to kill the Plasmodium in the liver. If this other medicine is not given, malaria can come back after months. It can even come back five years later.

The medicine used to kill malaria in the liver is primaquine. In southeast Asia, some P. vivax is resistant to primaquine. Most other places, primaquine works very well.

Some people get very sick from primaquine. Some people do not make enough of an enzyme in the blood. This enzyme is called Glucose-6-Phosphate-Dehydrogenase (Acronym G6PD). People who do not have enough have a disease called G6PD deficiency (or favism). People with G6PD-deficiency get very very sick if they take primaquine. It makes their red blood cells all die. This can even kill them. So people have to be tested to see if they have G6PD-deficiency before they take primaquine.

Medicines to kill P. vivax and P. ovale in the liver are not safe for pregnant women. So a pregnant woman must usually take chloroquine until she has her baby.

Treatment of falciparum malaria

Falciparum is the worst kind of malaria. Most people who die from malaria have falciparum.

Many people with falciparum malaria must be treated in a hospital. People with falciparum malaria should be treated in a hospital if they are:

Even people who are treated with medicines at home should stay with the doctor for 8 hours. This is to make sure they do not get sicker. It also makes sure they can take the medicines by mouth.

Falciparum malaria also has more resistance to medicines. This makes it much harder to treat. Falciparum malaria is always treated with two or more medicines. Doctors choose the medicines by where in the world the person got malaria. Different places have P. falciparum that is resistant to different medicines.

The most important resistance is chloroquine-resistance. In some places in the world, P. falciparum is killed by chloroquine. In some places it is chloroquine-resistant. This means chloroquine does not kill it. In these places quinine can be used.

If people are very sick and cannot swallow medicines, they get intravenous (acronym IV) medicine. Intravenous means given into a vein. The IV medicine used for very bad chloroquine-resistant falciparum malaria is quinine. If people got malaria in a place with no chloroquine-resistance other medicines can be used. But sometimes doctors still use IV quinine. This is to be very certain they will kill the P. falciparum.

If the P. falciparum is not chloroquine-resistant people do not usually take quinine. This is because quinine can make people sick. If people get sick from quinine, it is called Cinchonism. Symptoms of cinchonism are:

How to prevent malaria

Take medicine to keep from getting sick after a bite, especially in those parts of the world where people get malaria.

Control mosquitoes

Vector control is one way to stop malaria. Vector means an organism that carries an infectious disease to another organism. For malaria, the vector is the anopheles mosquito. It carries Plasmodium to people.

There are many ways to conduct a good vector control. The best ways are different in different places. This depends on the environment. It also depends on how much malaria is in the place. So the best way to do vector control in the United States is different than the best way to do vector control in South Africa.

The most used method of vector control is pesticides. These are chemicals that kill the mosquito. The first pesticide used for vector control was DDT (dichlorodiphenyltrichloroethane.) DDT was first used in World War II.

DDT worked very well for vector control. It killed mosquitoes. It did not make people very sick at the time it was used. It did not cost very much money. Other chemicals for vector control had not been invented yet.

In many places mosquitos became resistant to DDT. This meant that DDT did not work anymore in these areas. The places where mosquitoes are DDT-resistant are:

The EPA (Environmental Protection Agency) classifies DDT as a Persistent Bioaccumulative Toxin (PBT)meaning that it builds up over time in the bodies of plants,animals and humans.DDT can be passed on from water to fish or some plants, and consequently passed from plant/fish on to humans who may eat them.

Possible Harmful Effects include:

Possible human carcinogen(cancer causing agent)

Damage to the liver

Can cause liver cancer

Temporarily damages the nervous system

Damage to reproductive system

Scientists also worried that DDT was making people and animals sick. Scientists think it might cause hormones to not work right. It might also make people and animals have trouble reproducing (getting pregnant and making babies.) It killed a lot of wildlife too.

They learned that DDT stays in the environment for a long time. They learned also that DDT used in one place may go all over the world. DDT used in Africa may go to Europe. So people are worried that DDT used today will stay in the world for a long time. This is why DDT is not allowed to be used in farming anymore.

For these reasons, people mostly use other chemicals for vector control. Organophosphate or carbamate pesticides are used, like malathion or bendiocarb. These cost more money than DDT. And there are ways to control malaria that do not use chemicals at all.

Vector control is not the only way to stop malaria. And DDT is not the only chemical that can be used for vector control. The best way to stop malaria is to use a combination of methods. In some places, DDT may be a useful part of a program to stop malaria. This is why DDT is still allowed to be used for controlling malaria.

Keeping mosquitoes from biting

The mosquito that carries malaria comes more at dawn (when the sun comes up) and dusk (when the sun goes down.) Be most careful at these times.

Wear long pants and shirts with long sleeves.

Wear mosquitoes repellent (this is a chemical that mosquitoes do not like, so they do not bite.) Mosquitoes will bite through thin cloth. So repellent should be used on skin and clothes.

Pesticides can be used in rooms to kill mosquitoes.

When sleeping outside, people use a mosquito net. This is made from cloth that air can go through but keeps mosquitoes out. It is put over a bed where people sleep to keep mosquitoes out. Sometimes people also use it when they are not sleeping. It is best to use mosquito nets that have been treated with Permethrin, which repels and kills mosquitoes.

Taking medicine to not get sick

People can take medicine when they are in a place where there is malaria. This reduces the chances that they contract malaria. This is called prophylaxis.

Some people take prophylactic medicines for years. Many people in areas where there is malaria do not have the money to buy this medicine.

People who live where there is no malaria usually have not had malaria. The first case malaria is usually much worse. So people from places where there is no malaria may take prophylactic medicines when they go to places where there is malaria.

The kind of prophylactic medicines people take depends on where they are. This is because not all medicines work on the malaria in every place. Some Plasmodium are resistant. Even if the right medicine is used, it does not always work. Sometimes people get malaria even if they take prophylaxis. Sometimes this is because people do not take the medicine the right way. But even if it is taken right, it does not always work.

To make them work best, prophylactic medicines have to be taken the right way. The medicine should start before going to an area with malaria. Most medicines should be taken for 4 weeks after coming home. One medicine (Malarone) only needs to be used for one week after coming home.